Proposed model of K_ATP channel gating. Cartoon model of proposed K_ATP channel gating states and inactivation caused by rupture of CD-I contacts, based on cKir2.2 structures. Stabilized CD-I interactions (red spheres) in the C_O channel (modeled on the K62W mutant 5KUK) permits binding of ATP or PIP₂ to transition to either ATP-bound (C_A) or PIP₂ bound (3SPI, 5KUM; O) states. Rupture of the CD-I contacts (orange spheres) disengages the CD from the membrane and results in transition to the apo (C_I; 3JYC) state, to which ligands cannot bind.